ArticleEMBO molecular medicine2021
Upfront admixing antibodies and EGFR inhibitors preempts sequential treatments in lung cancer models.
Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Lung adenocarcinoma surfaceome remodeling with EGFR inhibitors uncovers placental alkaline phosphatase as a target for combination therapy.Cell reports. Medicine · 2025Article
- Strategies to Overcome Resistance to Osimertinib in EGFR-Mutated Lung Cancer.International journal of molecular sciences · 2025Review
- Review
- A bispecific antibody targeting EGFR and AXL delays resistance to osimertinib.Cell reports. Medicine · 2024Article
- Targeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor.Pharmacological reviews · 2023Review
- Resistance of Lung Cancer to EGFR-Specific Kinase Inhibitors: Activation of Bypass Pathways and Endogenous Mutators.Cancers · 2023Review
- L858R emerges as a potential biomarker predicting response of lung cancer models to anti-EGFR antibodies: Comparison of osimertinib vs. cetuximab.Cell reports. Medicine · 2023Article
- Stratification of non-small cell lung adenocarcinoma patients with EGFR actionable mutations based on drug-resistant stem cell genes.iScience · 2023Article
- Extracellular Vesicles and Epidermal Growth Factor Receptor Activation: Interplay of Drivers in Cancer Progression.Cancers · 2023Review
- Design and selection of optimal ErbB-targeting bispecific antibodies in pancreatic cancer.Frontiers in immunology · 2023Article
- IL-1 and senescence: Friends and foe of EGFR neutralization and immunotherapy.Frontiers in cell and developmental biology · 2022Review
- Polyclonal antibody-induced downregulation of HER1/EGFR and HER2 surpasses the effect of combinations of specific registered antibodies.Frontiers in oncology · 2022Article
- Review
- Article
- SNRPB is a mediator for cellular response to cisplatin in non-small-cell lung cancer.Medical oncology (Northwood, London, England) · 2021Article
- Upfront admixing antibodies and EGFR inhibitors preempts sequential treatments in lung cancer models.EMBO molecular medicine · 2021Article
- Targeting AXL in NSCLC.Lung Cancer (Auckland, N.Z.) · 2021Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Some antibacterial therapies entail sequential treatments with different antibiotics, but whether this approach is optimal for anti-cancer tyrosine kinase inhibitors (TKIs) remains open. EGFR mutations identify lung cancer patients who can derive benefit from TKIs, but most patients develop resistance to the first-, second-, and third-generation drugs. To explore alternatives to such whack-a-mole strategies, we simulated in patient-derived xenograft models the situation of patients receiving first-line TKIs. Monotherapies comprising approved first-line TKIs were compared to combinations with antibodies specific to EGFR and HER2. We observed uniform and strong superiority of all drug combinations over the respective monotherapies. Prolonged treatments, high TKI dose, and specificity were essential for drug-drug cooperation. Blocking pathways essential for mitosis (e.g., FOXM1), along with downregulation of resistance-conferring receptors (e.g., AXL), might underlie drug cooperation. Thus, upfront treatments using combinations of TKIs and antibodies can prevent emergence of resistance and hence might replace the widely applied sequential treatments utilizing next-generation TKIs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.